Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 6, 2006

Presenter: William F. ReginePresenter's Affiliation: University of Maryland, Baltimore, MDType of Session: Scientific

Background

Adenocarcinoma of the pancreas, even when resectable, has a poor prognosis. Failures occur both locoregionally and systemically.

Adjuvant treatment of resected pancreas adenocarcinoma is controversial. Although the ESPAC trial showed that adjuvant chemotherapy alone was superior to chemoradiation, this study has been widely criticized.

Chemoradiation (CRT) with 5FU has been a standard treatment in the U.S.

Gemcitabine (G) is active in pancreas cancer, and confers a survival benefit in the metastatic setting.

RTOG 9704 was designed to determine if the addition of G to postoperative adjuvant 5-FU CRT improved survival for patients with resected pancreatic adenocarcinoma.

Patients with pathologic stage T1-4, N0/1, M0 pancreatic adenocarcinoma status post gross total resection. The surgeon on this study reviewed all of the operative notes and pathology reports to confirm gross total resection.

original accrual goal was 330 patients, but rapid accrual allowed an amendment to look specifically at overall survival in pancreatic head tumors

Results

Arms were well balanced except for T-stage (T3/4 > for G, p=0.013)

Overall survival:

G significantly improved survival in pancreatic head tumors (n=380)

Median survival: 18.8 months G vs. 16.7 months 5-FU

3-yr survival: 31% G vs. 21% 5-FU

HR 0.79 (95% CI 0.63-0.99, p=0.047)

No significant difference when body/tail tumors included (n=442) (p=0.2)

Toxicity:

No significant difference in >Grade 3 non-hematologic toxicity

Grade 4 hematologic toxicity rate high in G arm

14% G arm vs. 2% 5-FU arm (p<0.0001)

No difference in febrile neutropenia/infection.

Ability to complete treatment per study was similar:

chemo (86%, 5-FU vs. 90%, G) and RT (85%, 5-FU vs. 88%, G)

Author's Conclusions

The addition of G to postoperative adjuvant 5-FU CRT significantly improves survival in pts with pancreatic head adenocarcinoma.

Clinical/Scientific Implications

Although the optimum adjuvant treatment for resected adenocarcinoma remains controversial, this study explored the best adjuvant chemotherapy to be combined with 5-FU sensitized CRT

This study was designed to evaluate adenocarcinoma of the pancreatic head as a primary endpoint. In this population there was a clear advantage to G of 5-FU for pre- and post-chemotherapy that sandwiched the CRT

The RTOG will adopt Gemzar followed by 5-FU/XRT followed by additional Gemzar as the standard for future clinical trials of adjuvant pancreatic cancer